Osteoarthritis is characterized by the progressive degeneration of the articular cartilage of the joints, ultimately leading to inflammation, pain, and impairment of mobility. In this proposal, we will address the molecular biology of osteoarthritis by means of manipulation of an in vitro chondrogenic cell culture system, application of gene knock-in technology to generate and then characterize mice that express mutated forms of cartilage types II and IX, and cartilage oligomeric matrix protein (COMP), and identification of candidate genes involved in cartilage development and maturation by means of differential gene expression profiling. The objective of the Morphology/Biomechanics Core (Core Leader: Rocky S. Tuan) is to provide state-of-the-art facilities and technologies for the characterization of the morphological, structural, gene expression profiling, and mechanical property testing of the cells and tissues generated from the Research Projects of the Program Project. The Morphology Component of the Core, will be responsible for routine histology, immunohistochemistry, in situ hybridization, ultrastructure, and confocal laser scanning microscopy, and will be carried out at the Orthopaedic Research Laboratory at Thomas Jefferson University. The Biomechanics Component will be supervised by Dr. Lori Setton in the Mechanical Engineering Department at Duke University, and will be responsible for the application of the osmotic loading technique to determine the mechanical properties of joint articular cartilage in the experimental mouse models that harbor the extracellular matrix gene mutations. Both Components of the core are staffed by experienced investigators with established, published experience in the application of these techniques in cartilage cells and tissues. The Morphology/Biomechanics Core therefore serves a vital function in the end-point analysis of cartilage structure and function, and is essential for the successful completion of the studies proposed in each of the Research Projects.